Conventional wall motion analysis of contrast ventriculograms assesses only that part of the wall that is tangential to the x-ray beam. To assess regional left ventricular function in three dimensions, a new computerized method based on densitometric analysis of digital subtraction left ventriculograms was developed and validated in nine open-chest dogs instrumented with a circumflex coronary artery occluder and sonomicrometers in the anterior and posterior walls. Each dog underwent digital subtraction ventriculography at baseline and at five levels (I to V) of dysfunction of the inferior wall induced by progressive stenoses of the circumflex coronary artery. The ventriculogram was divided into six segments around the end-diastolic center of gravity. Time-volume curves were obtained by densitometry in the normal anterior and ischemic inferior segments containing the sonomicrometers. From these curves, regional ejection fraction (R-EF), regional peak ejection rate (R-PER), and regional phase (R-PH) and amplitude (R-AMP) of the first Fourier harmonic were derived. From baseline to level V of dysfunction, myocardial systolic shortening determined by sonomicrometry decreased by 124 +/- 34% of control (mean +/- SD; p less than .001) in the ischemic wall, while it increased by 12 +/- 19% (NS) in the normal wall. At the same time, R-EF, R-PER, and R-AMP decreased in the ischemic segment by 65 +/- 12%, 46 +/- 30%, and 45 +/- 15% of control, respectively (all p less than .01), while they remained unchanged or increased in the normal segment. R-PH was delayed by 14 +/- 5% (p less than .01) in the ischemic segment, but remained unchanged in the normal segment, reflecting the asynchrony of regional left ventricular contraction during ischemia. Densitometric indexes of regional function correlated well with sonomicrometric systolic shortening both in normal and ischemic segments, with r values of .84 for R-EF, .80 for R-AMP, .64 for R-PER, and .55 for R-PH (all p less than .0001). Thus, densitometric analysis of digital subtraction left ventriculograms allows three-dimensional assessment of the extent, velocity, and synchrony of regional left ventricular contraction. Densitometric indexes of regional contraction correlate well with direct measurements of myocardial systolic shortening and are useful in quantitating regional left ventricular dysfunction.